Teclistamab, a IgG-4 bispecific antibody targeting BCMA and CD3, appears to be safe in patients with relapsed or refractory multiple myeloma, according to phase I data presented during the ASCO20 Virtual Scientific Program (Abstract 100).
According to study presenter Saad Z. Usmani, MD, FACP, of Levine Cancer Institute-Atrium Health, outcomes among patients with relapsed/refractory multiple myeloma are poor once the available classes of therapies are exhausted. The median overall survival of these patients is between 6 and 11 months, he said.
Among the promising new therapies for these patients are CAR T-cell therapies and bispecific antibodies, many of which target BCMA.
Among the promising new therapies for [patients with multiple myeloma] are CAR T-cell therapies and bispecific antibodies, many of which target BCMA.
Dr. Usmani and colleagues conducted a two-part study to test dosing, safety, and tolerability of teclistamab, a drug that redirects CD3-positive T cells to BCMA-expressing myeloma cells to induce cytotoxicity of the targeted cells.
The study included 78 patients with a median age of 62. Notably, patients age 70 or older made up 21% of the population. The median number of prior lines of therapy was six. No prior BCMA targeted therapy was allowed.
Of the 78 patients enrolled, 26 have ongoing treatment and 52 have discontinued treatment, primarily because of progressive disease.
There were two patient deaths from adverse events. There was one grade 5 respiratory failure in the setting of pneumonia deemed unrelated by an investigator, and one death due to COVID-19 that was not captured in the database at the time of data extraction.
According to Dr. Usmani, the safety profile was as one would expect for this population of patients with advanced, relapsed/refractory myeloma. Of note, grade 1/2 cytokine release syndrome (CRS) occurred in 44 patients. There was no high-grade CRS events following step-up dosing and no treatment discontinuation because of CRS.
Two dose-limiting toxicities occurred: a grade 4 delirium at the 20 µg/kg step-up dose and a grade 4 thrombocytopenia at the 180 µg/kg full dose. Additionally, 19% of patients had infections that were considered treatment-related by the investigator, Dr. Usmani noted.
Finally, six neurotoxicity events occurred; four of which were grade 1/2.
Response to teclistamab increased with higher doses of the drug. Overall responses were observed from the 38.4 µg/kg dose onward.
In the cohort of patients assigned the 270 µg/kg dose, the overall response rate was 67%, with half of these patients achieving a very good partial response or better. Additionally, seven of the eight responders at the 270 µg/kg dose were triple-class refractory, and five of eight were penta-drug refractory. Dr. Usmani noted that the efficacy data for the 720 µg/kg dose are not yet mature.
“The responses to teclistamab seem durable,” Dr. Usmani said. “Sixteen of 21 patients had ongoing response, and MRD-negative complete response at 10-6was achieved, with one durable beyond 12 months.”
The researchers observed that step-up dosing enabled transient decrease in peripheral T-cell counts and increased activation at full dose, consistent with the mechanism of action. This was consistently seen across all the dosing cohorts.
During his discussion of the abstract, Thomas Martin, MD, of University of California, San Francisco, said that this therapy had the potential of competing with CAR T-cell therapy for these patients.
According to Dr. Martin, what was most impressive about the study was not only the overall response rate of 70% in patients treated at higher dose levels, but the swimmers plot presented by Dr. Usmani (Figure).
“A significant number of patients are continuing response and responses look to depend over time, with one patient out as long as close to 19 months showing continuous response,” Dr. Martin said. “These are impressive data that we need to follow over time, and we need more patients followed.”
– Leah Lawrence
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